Pressure-sensitive adhesive for the skin and tapes or sheets for the skin made by using the same

ABSTRACT

The invention provides a pressure-sensitive adhesive for the skin excellent in pressure-sensitive adhesiveness to the human skin and repeelability therefrom, which does not cause the horny layer to be torn away in peeling and is lowly irritant to the skin; and tapes or sheets made by using the same. The pressure-sensitive adhesive is characterized by comprising (a) 100 parts by weight of a copolymer which is prepared from an olefinic macromonomer and a vinyl monomer and whose molecular weight (in terms of polystyrene and as determined by gel permeation chromatography (GPC)) has a two-peak distribution (with the proviso that when the copolymer is to be post-cured, the distribution is one as determined before the post cure) and (b) 20 to 250 parts by weight of a softener which is compatible with the copolymer and liquid or pasty at room temperature and has a boiling point of 250 or above (with the proviso that when the content of the softener (b) exceeds 80 parts by weight, the copolymer must be post-cured).

TECHNICAL FIELD

[0001] This invention relates to a tape or sheet for the skins,particularly relates to a tape or sheet which has good adhesiveness,re-peelability, and low skin irritation to the skin.

BACKGROUND ART

[0002] In the field of medical pressure sensitive adhesive tape, theneeds over the products which are gentle to the skin, and are free fromdamage of skin after repeated application to the skin. In this regard,there are some example tapes that are so-called low adhesion type tapemade from acrylics and rubber. However, these products also cause someproblems. After applying the tape to the skin, the adhesion increaseswith time, and the peeling of tape off the skin becomes difficult and apart of adhesive leaves on the skin after removal.

[0003] For example, the re-peelable medical adhesives which consist ofacrylic-acid and acrylic-ester copolymer are described in, JP 2700835,JP 3014188, Laid-open Publication H 11-269439 and Laid-open PublicationH 11-286664. The crosslinking of acrylic acid in the adhesive copolymerby isocyanate is described in the later 2 patents. However, theisocyanate is quite reactive for many compounds and often reacts withthe drugs in the adhesive. In this case, the crosslinking reactionitself is inhibited.

[0004] In Laid-open Publication H 10-251609, described is there-peelable type adhesive which consists of acrylic AB type blockcopolymer. However, The manufacturing of acrylic AB block adhesive hasmany technological problems and it is difficult to supply it at thepresent situation.

SUMMARY OF THE INVENTION

[0005] The present invention is invented in view of the problemsdescribed above, and its object is to provide a pressure-sensitiveadhesive for the skin excellent in pressure-sensitive adhesiveness tothe human skin and repeelability therefrom, which does not cause thehorny layer to be torn away in peeling and is lowly irritant to theskin; and tapes or sheets made by using the same.

[0006] The inventive pressure-sensitive adhesive for the skin ischaracterized by comprising (a) 100 parts by weight of a copolymer whichis prepared from an olefinic macromonomer and a vinyl monomer and whosemolecular weight (in terms of polystyrene and as determined by gelpermeation chromatography (GPC)) has a two-peak distribution (with theproviso that when the copolymer is to be post-cured, the distribution isone as determined before the post cure) and (b) 20 to 250 parts byweight of a softener which is compatible with the copolymer and liquidor pasty at room temperature and has a boiling point of 250 or above(with the proviso that when the content of the softener (b) exceeds 80parts by weight, the copolymer must be post-cured).

[0007] The inventive pressure adhesive tape or sheet for the skin ischaracterized in that the above pressure sensitive adhesive is disposedon at least of one surface of a substrate. In accordance with aparticular aspect of the present invention, skin permeable activeingredient is added to the adhesive.

DISCLOSURE OF THE INVENTION

[0008] The pressure sensitive adhesive for the skin of this inventioncomprises;

[0009] (a)100 parts by weight of a copolymer which is prepared from anolefinic macromonomer and a vinyl monomer and whose molecular weight (interms of polystyrene and as determined by gel permeation chromatography(GPC)) has a two-peak distribution (with the proviso that when thecopolymer is to be post-cured, the distribution is one as determinedbefore the post cure) and (b) 20 to 250 parts by weight of a softenerwhich is compatible with the copolymer and liquid or pasty at roomtemperature and has a boiling point of 250 or above (with the provisothat when the content of the softener (b) exceeds 80 parts by weight,the copolymer must be post-cured).

[0010] The olefinic macromonomer in this invention means the olefinicpolymer which has end unsaturated structure and has ability of radicalpolymerization. In other words, it is a polyolefin with a double bond atone terminal, having a nature of polymerization with other monomers. Thesaid polyolefin may be, polyethylene, polypropylene, ethylene-propylenecopolymer, and ethylene-butylene copolymer. As double bond group whichhas radical polymerization ability, vinyl group, acryloyl group, andallyl group are listed as examples.

[0011] The example of said olefinic macromonomer is an ethylene-butylenecopolymer end terminated with methyl methacrylate, brand name “KRATONLIQUID Polymer HPVM-1253” (made by Shell Chemical Company). Also, inLaid-open Publication H5 194631, in Laid-open Publication H5 247119, inLaid-open Publication H6 32847, and in Laid-open Publication H7 2928,described is polypropylene or ethylene-propylene random copolymer with(meth)acrylic acid alkylester terminal, such as methyl methacrylate.

[0012] The content of said olefinic macromonomer in said copolymer is20-65 weight %. When the content is lower, the concentration of softenerdissolved in copolymer decreases; while the content is higher, thecopolymer becomes gel at the time of polymerization, or the viscosity ofcopolymer becomes higher and would be difficult for handling.

[0013] The preferred examples of vinyl monomer for said copolymer arealkyl (meth)acrylate having 4-18 carbon atoms in the alkyl group, suchas butyl, pentyl, hexyl, heptyl, nonyl, decyl, dodecyl, and 2-ethylhexylgroup. The other examples are, (meth)acrylamide, N-vinyl-2-pyrrolidone,vinyl acetate, vinyl propionate, and alkoxyalkyl (meth)acrylate such asmethoxyethyl (meth)acrylate, and ethoxyethyl (meth)acrylate, and thelike. These monomers may be used independently and may be used together.The preferred content of alkyl (meth)acrylate is 20-40 weight% in saidcopolymer. When the content is higher, the cohesion of copolymer becomesweaker; and when the content is lower, the adhesion of copolymer becomesweaker.

[0014] Preferred copolymer is the one which is composed of one or moremonomers selected from the group comprising, alkyl (metha)acrylate,N-vinyl-2-pyrrolidone, vinyl acetate, and methoxyalkyl acrylate. Thepreferred content of above monomer(s) is 10-40 weight %. When thecontent is higher, the adhesion of said copolymer decreases; while thecontent is lower, the solubility of drug in said copolymer decreases.

[0015] For the purpose of enabling post-crosslinking of said copolymer,the vinyl monomers which has a functional group may be used togetherwith the above-mentioned vinyl monomers. As the vinyl monomer which hasfunctional group, for example, the acrylic monomer which has hydroxylgroup, carboxyl group, glycidyl group, and amino group, or the like, areused. If the content of the vinyl monomer which has the above-mentionedfunctional group decreases, the crosslinking ability of copolymerdecreases; while the content increases, the adhesion of copolymerdecreases. So that, the content in copolymer is preferably 0.5-25 weight%, more preferably 0.8-20%.

[0016] In the adhesive of this invention, a crosslinking agent may beadded for the purpose of increasing the holding power of said copolymerand the softener. The examples of crosslinking agent are, metal chelatecompound such as aluminum acetylacetonate, metal Alcoh-late such astetrabutyl titanate, acid chloride such as adipodichloride, polyaminesuch as diaminohexane, polyisocyanate, melamine resin, and the like.

[0017] If the above-mentioned crosslinking agent content decreases, thecrosslinking reaction does not proceed fully; while the contentincreases, the adhesion of composite decreases. So that 0.01-2.0 weightparts is added to said copolymer of 100 weight parts.

[0018] In this invention, however, it is needed for the MWD of saidcopolymer weight (in terms of polystyrene and as determined by GPC) ofsaid copolymer has a two-peak distribution, (with the proviso that whenthe copolymer is to be post-cured, the distribution is one as determinedbefore the post cure). If the MWD of polymer does not have two peaks, itbecomes impossible to realize the re-peelability and low skinirritation, because the balance of adhesive strength and cohesive forcecollapses.

[0019] Regarding the two peaks of MWD of said copolymer, 200,000-800,000is the desirable high molecular weight peak, and 2,000-7,000 is thedesirable low molecular weight peak. The realization of there-peelability to the skin and low irritation becomes difficult when thepeaks go out of the above range.

[0020] Regarding the manufacturing method of said copolymer, forexample, the mixture of monomers is dissolved in solvents, such astoluene, ethyl acetate, tetrahydrofuran, and methyl ethyl ketone,together with a polymerization initiator. It is heated under nitrogenatmosphere. As the above-mentioned polymerization initiator, peroxidessuch as benzoyl peroxide, azo compound such as azobisisobutyronitrile,and the like, are used. The weight average molecular weight ofcopolymer(A) is ca. 200,000 to 2,000,000.

[0021] The softener used in this invention is to give the properties ofgood adhesiveness, good re-peelability, and low skin irritation, to saidcopolymer. The softening agent in this invention has properties of (1)liquid or pasty at room temperature, (2) good compatibility to saidcopolymer, (3) boiling temperature of above 250° C. The examples are,hydrocarbon such as liquid paraffin, squalane, lanolin; and ester suchas isopropyl myristate, ethyl laurate, isopropyl adipate, octylpalmitate, isopropyl palmitate, ethyl oleate, octyldodecyl myristate,cetyl isooctanoate, octyldodecyl oleate, glyceryl tri-2-ethylhexanate,neopentyl glycol diethylhexanoate, octyldodecyl lactate, anddiisostearyl malate.

[0022] These may be used independently, and may be used together andmore than one softening agents selected from the group which consists ofisopropyl myristate, isopropyl palmitate, ethyl oleate, octyldodecylmyristate, cetyl isooctanoate, octyldodecyl oleate, glyceryltri-2-ethylhexanate, neopentyl glycol diethylhexanoate, octyldodecyllactate, and diisostearyl malate.

[0023] The amount of addition of said softening agent is 20-250 weightparts to said copolymer of 100 weight parts, and preferably 30-150weight parts. When the amount of addition decreases, the adhesivestrength becomes stronger and the skin irritation increases; while theamount increases, and cohesive force declines. The cohesive force is toolow to be useful when the amount of addition of said softening agentexceeds 80 weight parts. In this case, it is necessary to make saidcopolymer crosslink using the above-mentioned crosslinking agent.

[0024] In this invention, tackifier can be added to copolymer compositefor the purpose of adjustment of adhesive power or cohesive force, andthe amount of addition is 5-30 weight parts to said copolymer of 100weight parts. The examples of tackifier are, rosin ester, polyterpeneresin, and hydrocarbon resin, and the like.

[0025] Skin-permeable active ingredient can be added into said compositein this invention. The examples are, anti-inflammatory drug such asketoprofen and piroxicam, antihypertension, anesthetic, antibacterial,antifungal, vasodilator, antihistamine, cerebral circulationimprovement, sex hormone such as estradiol, vitamins, whitening agent,moistening agent, and the like.

[0026] All drugs and cosmetic ingredients can be used in this inventionso far as they can permeate into the skin. They can be dissolved or canbe dispersed in said adhesive. When, the drug or cosmetic ingredient hashydroxyl group and/or carboxyl group, the crosslinking method should becareful from the viewpoint of stability of drug.

[0027] The preferred tape or sheet of the present invention has theconstruction of (flexible backing material/adhesive) or (flexiblebacking material/adhesive/release liner). In terms of adhesive strengthof the tape to the skin, the tape that gives peeling force of 50-400g/25 mm width to bakelite board is preferred.

[0028] Many manufacturing process of the tape of this invention may beadopted. For example, said copolymer, said softening agent, saidcrosslinking agent if needed, a drug or a cosmetic ingredient, etc., aremixed to obtain the coating solution. If needed, ethyl acetate, toluene,etc. are added to the solution for the viscosity adjustment. Thusobtained coating solution is coated onto release liner with a thicknessof 0.01-0.2 mm (in terms of dry adhesive thickness). After removing thesolvent by heating, the sheet is laminated onto flexible backingmaterial.

[0029] As for the above-mentioned flexible backing material, plasticfilm such as polyethylene terephthalate and polypropylene, nonwovenfabric, paper, foam, and the like are used.

[0030] As for the above-mentioned release liner, The siliconized film orsheet selected from polyethylene terephthalate, polypropylene, paper,and the like are used.

BEST MODE FOR CARRYING OUT THE INVENTION

[0031] Then, examples of the present invention are described. Hereafter,“part” means “weight part” and “%” means “weight %.”

Example 1

[0032] Under nitrogen atmosphere, olefinic macromonomer, KRATON LIQUIDPolymer HPVM-1253 (Shell Chemical Company) of 40 parts, 2-ethylhexylacrylate of 30 parts, N-vinyl-2-pyrrolidone of 20 parts, and2-hydroxyethyl acrylate of 10 parts, were polymerized at 70° C. withazobisisobutironitrile of 0.05 parts as initiator in ethyl acetate of200 parts, for 24 hours, and the copolymer solution was prepared.

[0033] To the copolymer solution of 100 parts (in terms of solid), 30parts of isopropyl myristate was added, thus giving the coatingsolution. The viscous solution thus obtained was coated ontopolyethylene terephthalate release liner of 75-micrometer thickness, thethickness of coating solution was adjusted to be adhesive layer of 80micrometer (in terms of solid). The coated solution was dried for 20minutes at 80° C., and the adhesive sheet was prepared. The polyethyleneterephthalate film with thickness of 40 micrometer was laminated on thisadhesive layer, and the skin tape was prepared.

[0034] The MWD of copolymer obtained by using GPC had two peaks. Themolecular weight of the higher molecular peak was 427,000, and themolecular weight of lower molecular weight peak was 3,300.

[0035] The details of MWD measurement were as follows;

[0036] The copolymer solution was dried, and the obtained solidcopolymer was dissolved into THF with a concentration of 3.0 mg/ml, asthe sample solution. The apparatus used was LC-08, Japan Bunnseki Kogyo,with three columns connected in series, namely Shima-pack GPC806, 843,and 801, Shimadzu Seisakusyo, Japan. After filtration, the samplesolution of 300 microliter was chromatographed. The eluent was THF withthe flow rate of 1 ml/min. The ambient temperature was 40° C., and therefractive index detector was used. The chromatogram thus obtained wasanalyzed with the calibration curve obtained from polystyrene standardssamples. The MWD was determined in terms of polystyrene. The sameprocedure was adopted for every example and comparative example.

Example 2

[0037] The same procedure as Example 1 was repeated to obtain the skinsheet, except that the amount of isopropyl myristate was changed to 50parts.

Example 3

[0038] The same procedure as Example 1 was repeated to obtain the skinsheet, except that the amount of isopropyl myristate was changed to 70parts.

Example 4

[0039] The same procedure as Example 1 was repeated to obtain the skinsheet, except that the amount of isopropyl palmitate of 100 partsinstead of isopropyl myristate of 30 parts was used, and that tetrabutyltitanate of 2 parts was added as the crosslinker into the adhesivesolution.

Example 5

[0040] The same procedure as Example 4 was repeated to obtain the skinsheet, except that the amount of isopropyl palmitate was changed to 150.

Example 6

[0041] The same procedure as Example 4 was repeated to obtain the skinsheet, except that the amount of isopropyl palmitate was changed to 200.

Comparative Example 1

[0042] Under nitrogen atmosphere, 2-ethylhexyl acrylate of 95 parts,acrylic acid of 5 parts were polymerized at 70° C. withazobisisobutironitrile of 0.05 parts as initiator in ethyl acetate of200 parts for 24 hours, and the copolymer solution was prepared.

[0043] To the copolymer solution of 100 parts (in terms of solid), 15parts of isopropyl myristate was added, thus giving the coatingsolution. The solution obtained was coated onto polyethyleneterephthalate release liner of 75-micrometer thickness, the thickness ofcoating solution was adjusted to be adhesive layer of 80 micrometer (interms of solid). The coated solution was dried for 20 minutes at 80° C.,and the adhesive sheet was prepared. The polyethylene terephthalate filmwith thickness of 40 micrometer was laminated on this adhesive layer,and the skin tape was prepared.

[0044] The MWD of copolymer obtained by using GPC showed one peak. Themolecular weight of peak was 327,000.

Comparative Example 2

[0045] The same procedure as Comparative example 1 was repeated toobtain the skin sheet, except that the amount of isopropyl myristate waschanged to 50 parts.

Comparative Example 3

[0046] The same procedure as Comparative example 1 was repeated toobtain the skin sheet, except that the amount of isopropyl myristate waschanged to 70 parts.

Comparative Example 4

[0047] The same procedure as Example 1 was repeated to obtain the skinsheet, except that the isopropyl palmitate of 100 parts was used insteadof isopropyl myristate of 30 parts.

(Comparative Example 5

[0048] The same procedure as Comparative example 4 was repeated toobtain the skin sheet, except that the amount of isopropyl palmitate was150 parts.

Comparative Example 6

[0049] The same procedure as Comparative example 4 was repeated toobtain the skin sheet; except that the amount of isopropyl palmitate was300 parts, and that tetrabutyl titanate of 0.2 parts as the crosslinkerwas added.

Example 7

[0050] The same procedure as Example 1 was repeated to obtain the skinsheet, except that ethyl oleate of 50 parts instead of isopropylmyristate of 30 parts and rosin of 10 parts (tackifier) were added intothe copolymer solution.

Comparative Example 7

[0051] The same procedure as Example 1 was repeated to obtain the skinsheet, except that the softener was removed.

Example 8

[0052] Under nitrogen atmosphere, olefin macromonomer, KRATON LIQUIDPolymer HPVM-1253 (Shell Chemical Company) of 50 parts, butyl acrylateof 23 parts, methoxyethyl acrylate of 26 parts, and acrylic acid of 1parts were polymerized at 70° C. with benzoyl peroxide of 0.02 parts asinitiator in ethyl acetate of 100 parts for 24 hours, and the copolymersolution was prepared.

[0053] To the copolymer solution of 100 parts (in terms of solid), 50parts of octyldodecyl lactate, and 8 parts of estradiol was added, thusgiving the coating solution. The solution obtained was coated ontopolyethylene terephthalate release liner of 75-micrometer thickness, thethickness of coating solution was adjusted to be adhesive layer of 80micrometer (in terms of solid). The coated solution was dried for 20minutes at 80° C., and the adhesive sheet was prepared. The polyethyleneterephthalate film with thickness of 40 micrometer was laminated on thisadhesive layer. After aging at 40° C. for 2 days, the skin tape wasprepared.

[0054] The MWD of copolymer obtained by using GPC showed two peaks. Themolecular weight of the higher molecular peak was 524,000, and themolecular weight of lower molecular weight peak was 4,300.

Example 9

[0055] The same procedure as Example 1 was repeated to obtain the skinsheet, except that the amount of isopropyl myristate was of 100 parts,and that tetrabutyl titanate of 0.2 parts was added, and that ketoprofenof 20 parts was added.

Example 10

[0056] Under nitrogen atmosphere, olefin macromonomer, KRATON LIQUIDPolymer HPVM-1253 (Shell Chemical Company) of 50 parts, 2-ethylexylacrylate of 30 parts, vinyl acetate of 18 parts, and acrylic acid of 2parts were polymerized at 70° C. with benzoyl peroxide of 0.02 parts asinitiator in ethyl acetate of 100 parts for 24 hours, and the copolymersolution was prepared. To the copolymer solution of 100 parts (in termsof solid), 50 parts of diisostearyl malate, and 5 parts of piroxicam wasadded, thus giving the coating solution. The following procedure was asthe same as that of Example 8, and the skin tape was prepared.

[0057] The MWD of copolymer obtained by using GPC showed two peaks. Themolecular weight of the higher molecular peak was 412,000, and themolecular weight of lower molecular weight peak was 4,200.

Example 11

[0058] The same procedure as Example 8 was repeated to obtain the skinsheet, except that cetyl isooctanoate of 100 parts instead ofoctyldodecyl lactate of 50 parts was added and that polyisocyanate,Koronate HL, Nippon Polyurethane, Japan, of 1 part was added.

Example 12

[0059] Under nitrogen atmosphere, olefin macromonomer, KRATON LIQUIDPolymer HPVM-1253 (Shell Chemical Company) of 50 parts, dodecyl acrylateof 40 parts, stearyl acrylate of 4 parts, vinylpyrollidone of 15 parts,hydroxyethyl acrylate of 10 parts, and acrylic acid of 1 part werepolymerized at 70° C. with benzoyl peroxide of 0.02 parts as initiatorin ethyl acetate of 150 parts for 24 hours, and the copolymer solutionwas prepared.

[0060] To the copolymer solution of 100 parts (in terms of solid), 50parts of tri-2-ehylhexanate and 4 parts of piroxicam were added, thusgiving the coating solution. The following procedure was the same asthat of Example 8 and the skin tape was prepared.

[0061] The MWD of copolymer obtained by using GPC showed two peaks. Themolecular weight of the higher molecular peak was 472,000, and themolecular weight of lower molecular weight peak was 4,200.

Comparative Example 8

[0062] Styrene isoprene rubber, Craton 1107 (Craton polymer Japan), of100 parts, hydrogenated rosin ester of 100 parts, liquid paraffin of 30parts and ketoprofen of 4 parts, were dissolved in toluene of 500 parts,and the coating solution was obtained. After that, the same coatingprocedure as Comparative example 1 was adopted and the skin sheet wasobtained.

Comparative Example 9

[0063] Under nitrogen atmosphere, olefin macromonomer, KRATON LIQUIDPolymer HPVM-1253 (Shell Chemical Company) of 70 parts, 2-ethylhexylacrylate of 10 parts, and N-vinyl-2-pirrolidone 20 parts werepolymerized at 70° C. with azobisisobutyronitrile of 0.025 parts asinitiator in ethyl acetate of 200 parts. At 5 hours after beginning ofthe polymerization, the gelation of polymer solution began and after 7hours the polymerization was stopped because of severe gelation.

Comparative Example 10

[0064] Under nitrogen atmosphere, olefin macromonomer, KRATON LIQUIDPolymer HPVM-1253 (Shell Chemical Company) of 15 parts, 2-ethylhexylacrylate of 60 parts, n-vinyl-2-pyrollidone of 20 parts, and acrylicacid of 5 parts were polymerized at 70° C. for 24 hours withazobisisobutyronitrile of 0.025 parts as initiator in ethyl acetate of200 parts, and the copolymer solution was prepared.

[0065] To the copolymer solution of 100 parts (in terms of solid), 15parts of isopropylmyristate was added, thus giving the coating solution.The following procedure was the same as that of Example 1 and the skintape was prepared.

[0066] The MWD of copolymer obtained by using GPC showed one peak. Themolecular weight of the peak was 583,000.

Comparative Example 11

[0067] The same procedure as Comparative example 10 was repeated toobtain the skin sheet, except that the amount of isopropyl myristate was50 parts.

Comparative Example 12

[0068] The same procedure as Comparative example 10 was repeated toobtain the skin sheet, except that the amount of isopropyl myristate was70 parts.

Evaluation

[0069] The following examinations were performed after storing the aboveobtained samples for two weeks under 40° C. and 75% of humidityconditions.

[0070] (Adhesive Strength Examination)

[0071] The tape sample cut in width of 25 mm was stuck on the bakeliteboard. After pressing the tape twice with a roller of 300 g, themeasurement of 180 degrees peel strength was carried out with thepeeling speed of 300 mm/min. Thus obtained results are shown in Table 1.

[0072] (Paper Removal Test)

[0073] The tape sample cut in width of 25 mm was stuck on the newspaper.After pressing the tape twice with a roller of 300 g of load, the tapewas peeled off with 300 mm/min speed. Both of the removal of paper (orpaper torn away) by the adhesive and the cohesion failure of adhesivewere examined. Thus obtained results are shown in Table 1. TABLE 1Softening Agent Adhesion Paper removal (Amount, Cross Strength PaperTorn Cohesion Ex. No wt. Part) linker (g/25 mm) Away Failure Ex. 1 IPM(30) − 220 Not observed Not observed Ex. 2 IPM (50) − 190 Not observedNot observed Ex. 3 IPM (70) − 160 Not observed Not observed Ex. 4 IPP(100) + 230 Not observed Not observed Ex. 5 IPP (150) + 200 Not observedNot observed Ex. 6 IPP (200) + 190 Not observed Not observed Ex. 7 EO(50) − 250 Not observed Not observed Ex. 8 OL (50) − 170 Not observedNot observed Ex. 9 IPM (100) + 200 Not observed Not observed Ex. 10 SM(50) − 130 Not observed Not observed Ex. 11 SO (100) + 190 Not observedNot observed Ex. 12 GE (50) − 100 Not observed Not observed Co. Ex. 1IPM (15) − 1350 Observed Not observed Co. Ex. 2 IPM (50) − * # ObservedCo. Ex. 3 IPM (70) − * # Observed Co. Ex. 4 IPP (100) − * # Observed Co.Ex. 5 IPP (150) − * # Observed Co. Ex. 6 IPP (300) + 0 () Not observedNot observed Co. Ex. 7 (0) − 890 Observed Not observed Co. Ex. 8 Rosin(30) − 1250 Observed Not observed Co. Ex. 10 IPM (15) − 1440 ObservedNot observed Co. Ex. 11 IPM (50) − * # Observed Co. Ex. 12 IPM (70) − *# Observed

[0074] Ex. (Example), Co.Ex. (Comparative Example) IPM (Isopropylmyristate), IPP (Isopropyl palmitate), EO (Ethyl oleate),

[0075] OL (Octyldodecyl lactate), SM (Diisostealy malate), SO (cetylisooctanoate),

[0076] (GE) tri-2-ehylhexanate.

[0077]  Because of the cohesive failure, the determination could not beperformed.

[0078] # Major part of adhesive left on the paper.

[0079]

The bleeding of IPP on the adhesive was severe.

[0080] The skin adhesives from Comparative examples 2-6 and 11-12 weretoo soft so that the adhesive showed the cohesion failure. When it wasapplied on the skin, a part of adhesive left on the skin after theremoval. Hence these adhesives were unsuitable as skin adhesive, thesubsequent skin irritation test was not carried out for these adhesives.

[0081] (Skin Irritation Study)

[0082] The sample tape with a diameter of 2.0 cm was applied to theinside of three volunteers' upper arm. It was removed after 24-hours,and the average value of skin irritation just after the removal wascalculated according to the irritation index that shown below. Theresults are shown in Table 2.

[0083] <Irritation index >

[0084] 0: No skin irritation,

[0085] 1: Very slight irritation,

[0086] 2: Slight irritation

[0087] 3: Irritation

[0088] 4: Severe irritation TABLE 2 Softening Agent Skin Ex. No (Amount,Wt. Part) Irritation Ex. 1 IPM (30) 0.33 Ex. 2 IPM (50) 0.33 Ex. 3 IPM(70) 0.67 Ex. 4 IPP (100) 0.33 Ex. 5 IPP (150) 0.67 Ex. 6 IPP (200) 0.33Ex. 7 EO (50) 0.67 Ex. 8 OL (50) 0.67 Ex. 9 IPM (100) 0.33 Ex. 10 SM(50) 0.33 Ex. 11 SO (100) 0.67 Ex. 12 GE (50) 0.33 Co. Ex. 1 IPM (15)1.67 Co. Ex. 7 — (0) 1.33 Co. Ex. 8 Liquid paraffin (30) 2.00 Co. Ex. 10IPM (15) 2.00

[0089] (Drug Stability Test)

[0090] After storage of the sample tape, the drug content in tapesamples were determined. Firstly, the theoretical drug content in apatch of 2.0 cm diameter was calculated by measuring the weight of thepatch. Then, it was put into 50 cc ethanol for drug extraction at 36° C.for 24 hours. The drug content was determined with HPLC.

[0091] <HPLC Condition>

[0092] Detector: UV photometer (wavelength=230-280 nm)

[0093] Column: ODS type, inner diameter of 4-8 mm, length of 50-300 mm

[0094] Column temperature: 40° C.

[0095] Eluent:

[0096] For estradiol . . . Acetonitrile:water(55:45, volume ratio)

[0097] For ketoprofen . . . Acetonitrile:water(pH3.0)(60:40, volumeratio)

[0098] For piroxicam . . . Acetonitrile:water(pH3.0) (42:58, volumeratio)

[0099] The results are shown in Table 3. TABLE 3 Ex. No.(Content-measured)/(Content-theoretical) Ex. 8 0.96 Ex. 9 0.94 Ex. 100.98 Ex. 11 0.98 Ex. 12 0.97

[0100] Content-measured (Drug in patch determined with HPLC)

[0101] Content-theoretical (Drug in patch calculated)

[0102] The content of drug in all example tapes did not decrease duringthe storage time. This indicates that above adhesives are suitable forloading the drugs.

EFFECTS OF THE INVENTION

[0103] The present invention provides a pressure-sensitive adhesive ischaracterized by comprising (a) 100 parts by weight of a copolymer whichis prepared from an olefinic macromonomer and a vinyl monomer and whosemolecular weight has a two-peak distribution, and (b) 20 to 250 parts byweight of a softener which is compatible with the copolymer and liquidor pasty at room temperature and has a boiling point of 250 or above(with the proviso that when the content of the softener (b) exceeds 80parts by weight, the copolymer must be post-cured). The tape or sheetfor the skin made from the above adhesive is re-peelable and does notgive damage to the skin. Therefore, the tape or sheet of this inventionis quite useful for dressing tape, medicated tape, and cosmetic sheet.

1. A transdermal adhesive comprising; (a) 100 parts by weight of acopolymer which is prepared from an olefinic macromonomer and vinylmonomers and whose molecular weight (in terms of polystyrene and asdetermined by gel permeation chromatography (GPC)) has a two-peakdistribution (with the proviso that when the copolymer is to bepost-cured, the distribution is one as determined before the post cure);and (b) 20 to 250 parts by weight of a softener which is compatible withthe copolymer and liquid or pasty at room temperature and has a boilingpoint of 250° C. or above (with the proviso that when the content of thesoftener (b) exceeds 80 parts by weight, the copolymer must bepost-cured).
 2. A transdermal adhesive composition comprising: (1) apressure-sensitive adhesive comprising: (a) 100 parts by weight of acopolymer which is prepared from an olefinic macromonomer and a vinylmonomer and whose molecular weight (in terms of polystyrene and asdetermined by gel permeation chromatography (GPC)) has a two-peakdistribution (with the proviso that when the copolymer is to bep)ost-cured, the distribution is one as determined before the postcure), wherein the higher molecular weight peak is within 200,000 to800,000 while the lower molecular weight peak is within 2,000 to 7,000;and (b) 20 to 250 parts by weight of one or more kinds of softenerselected from the group consisting of isopropyl myristate, isopropylpalmitate, ethyl oleate, octyldodecyl myristate, cetyl isooctanoate,octyldodecyl oleate, glyceryl tri-2-ethylhexanate, neopentyl glycol,diethylhexanoate, octyldodecyl lactate, and diisostearvl malate (withthe proviso that when the content of the softener (b) exceeds 80 partsby weight, the copolymer must be post-cured); and (2) one or more of adrug or cosmetic active ingredient being dissolved or dispersed in saidpressure-sensitive adhesive.
 3. The transdermal adhesive according toclaim 1 or 2, wherein the content of macromonomer in said copolymer (a)is 20 to 65 weight %.
 4. The transdermal adhesive according to any oneof claims 1 to 3, wherein the vinyl monomer of said copolymer (a) is oneor more monomers selected from the group comprising, alkyl(metha)acrylate, N-vinyl-2-pyrrolidone, vinyl acetate, and methoxyalkylacrylate.
 5. The transdermal adhesive according to claim 4, wherein saidalkyl (metha)acrylate is selected from the group of butyl acrylate,2-ethylhexyl acrylate, dodecyl acrylate, and stearyl acrylate, andN-vinyl-2-pyrrolidone, vinyl acetate, and methoxyalkyl acrylate.
 6. Thetransdermal adhesive according to any one of claims 1 to 5, wherein thecontent of said alkyl (metha)acrylate is 20 to 40 weight % and thecontent of one or more monomers selected from the group comprising,N-vinyl-2-pyrrolidone, vinyl acetate, and methoxyalkyl acrylate is 10 to40 weight %.
 7. The transdermal adhesive according to claim 1, whereinsaid copolymer (a) contains 0.1 to 25 weight % of vinyl monomer having afunctional group.
 8. The transdermal adhesive according to claim 7,wherein said functional group is selected from carboxyl group, hydroxylgroup and glycidyl group.
 9. The transdermal adhesive according to anyone of claim 7 or 8, wherein 0.01 to 2.0 weight parts of crosslinkingagent is added to 100 weight parts of said copolymer.
 10. Thetransdermal adhesive according to claim 9, wherein said crosslinkingagent is selected from metal chelate compound, metal alcohlate, acidchloride, polyamine, polyisocyanate, and melamine resin.
 11. Thetransdermal adhesive according to claim 1, wherein said softener isselected from the group of isopropyl myristate, isopropyl palmitate,ethyl oleate, octyldodecyl myristate, cetyl isooctanoate, octyldodecyloleate, glyceryl tri-2-ethylhexanate, neopentyl glycol,diethylhexanoate, octyldodecyl lactate, and diisostearyl malate.
 12. Thetransdermal adhesive according to claim 1, wherein 5 to 30 weight partsof tackifier is added to 100 weight parts of said copolymer (a).
 13. Atape or sheet for the skin wherein said adhesive according to 1, is laidon at lease one surface of a backing material.
 14. A tape or sheet forskin, comprising said transdermal adhesive according to claim 1, andfurther comnrising a skin-permeable active ingredient, wherein saidtransdermal adhesive is laid on at least one surface of a backingmaterial.
 15. The tape or sheet for skin according to claim 14, whereinsaid skin-permneable active ingredient is a drug or a cosmeticingredient.